The development of most chronic diseases is a multifactorial process involving issues of susceptibility (from genetic or nutritional factors) and environmental exposures. This project focuses on hormonally-mediated diseases which particularly impact women and minority populations. 1)Data (including blood and urine samples) have been collected from 110 women participating in a longitudinal study of perimenopausal bone density. These data will be analyzed to identify environmental factors (e.g., dietary calcium, estrogen use) which may modify genetic influences (e.g., vitamin D receptor polymorphisms) on osteoporosis; undercarboxylated osteocalcin and vitamin K1 status will also be assessed. 2)We are developing a study of the long-term effect of prenatal DES exposure on bone, involving follow-up of 200 children born in 1951-2 as part of a randomized, controlled trial. This study will help elucidate the role of estrogens during early stages of development on adult bone density. 3)Data analysis is continuing in a cohort study of 1000 women who participated in a prospective study of menstrual cycle patterns begun in 1935. We have completed an analysis of factors, such as alcohol use, physical activity, and smoking, associated with cycle length, variability, and bleeding duration. This analysis supports the influence of these environmental factors on estrogen-related processes, and thus may help elucidate their etiologic role in specific diseases. To follow- up these findings we are analyzing the menstrual and reproductive risk factors for cardiovascular disease and for bone fractures within this cohort. 4)A population-based case-control study of 300 systemic lupus erythematosus (SLE) patients is being developed to examine the role of infectious diseases, nutritional status, and genetic susceptibility in this endocrine-related autoimmune disorder.